DESCRIPTION (Verbatim from Applicant's Abstract): Laser treatment of hypervascular cutaneous malformations such as port wine stain (PWS) lesion is based or selective photocoagulation of subsurface targeted blood vessels without inducing thermal damage to the superficial skin layers. The principal investigator and his collaborators are interested in development and optimization of cryogen spray cooling (CSC) to protect the superficial skin layers from thermal injury during high laser light dosages (2 10 J.cm about ), and long pulses (> 0.5 ms) for more efficient and effective clinical management of PWS patients. for more efficient and effective clinical management of PWS patients. To fully explore the potentials of CSC and optimize its efficiency under the most severe laser irradiation conditions that may be required for more effective treatment protocols, further studies aimed at understanding the thermodynamics and heat transfer processes associated with CSC are required. The specific objectives of this proposal are to: ( I ) develop mathematical models to predict skin internal temperature distributions following cryogen spurt termination by solving an inverse heat transfer formulation with a one dimensional inversion algorithm and subsequent, computation of temperature profiles in response to high incident light dosages and long laser pulses when specifically utilized in conjunction with CSC; (2) utilize various cryogen delivery s' about'ems to produce a wide range of droplet size, and study the subsequent thermal response of the substrate (i.e., an in-vitro epoxy resin model, and ex-vivo human skin samples, (3) conduct CSC and laser irradiation of ex-vivo human skin samples to determine optimum cooling parameters for epidermal protection under high incident light dosages and long pulse durations, and validate results of the mathematical modeling; (4) perform in-vivo experiments using the chicken comb animal model to investigate the utility of CSC in protecting the superficial tissue layers while allowing laser induced photocoagulation of dermal blood vessels; (5) utilize the information obtained from the aforementioned thermodynamic studies at theoretical, in-vitro, ex-vivo, and in-vivo animal model levels in conjunction with one-dimensional inversion of pulsed photothermal radiometry (PPTR) data to "recommend" optimum CSC and laser irradiation parameters for a specific lesion and skin type; and (6) Conduct clinical studies in PWS patients to evaluate the effectiveness of CSC in conjunction with laser irradiation using high incident dosage, longer pulses and wavelengths, and correlate the therapeutic outcome with the "recommended CSC and irradiation parameters."